A program to study the cell biology and immunology of normal and neoplastic mammary glands has been developed. Using transplantation methods with the aid of histocompatibility markers, mammary parenchyma or parenchymal-stromal combinations composed of cells of different genotypes will be studied to analyze cell types and cell interactions during neoplastic progression and host responses to cryptic antigenic cells. Three separate cell populations comprising normal breast give rise to 3 classes of neoplasia. Normal cell associations are required by neoplastic cells of some types during neoplastic progression and metastasis. The correlation of cell type of origin, cellular composition, and interdependence of cells with histopathology, growth, and metastatic characteristics will be studied. The afferent limb of the cytotoxic cellular immune response is blocked by anatomical or physiological factors in some epithelial, endocrine, and neoplastic tissues. Persistent antigenic cells induce specific suppressor responses simulating normal self tolerance. Qualitatively different immune responses susceptible or resistant to this suppression exist. Suppressor responses permit allografting without general immuno-depression. Immune responses resistant to suppression cause regression of established neoplasms. Methods for induction of natural suppression of allograft immunity and for induction of effective immunity to various types and stages of mammary neoplasia will be studied.